Notopterol alleviates the progression of osteoarthritis: An in vitro and in vivo study

• Published in: Cytokine (Philadelphia, Pa.) Vol. 169; p. 156309
• Main Authors: Qu, Yuhan, Qiu, Lu, Qiu, Hui, Shen, Yue, Tang, Min, Huang, Yuehui, Peng, Yi, Wang, Jun, Fu, Qiang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2023
• Subjects: Apoptosis vivo; C28/I2 cells; Inflammation; Notopterol; Osteoarthritis; Bcl-2; NO; Apoptosis vivo; COX-2; HO-1; RIPA; BSA; OA; PI3K; ADAMTS-5; Nrf2; NSAIDs; CCK-8; iNOS; PBS; PGE2; MIA; H&E; MMPs; qRT-PCR; AKT; Inflammation; IL-1β; ECM; OARSI; RA; SDS-PAGE; Notopterol; TNF-α; PMSF; C28/I2 cells; CEX; ROS; Bax; JAK2/STAT3; GAPDH; Osteoarthritis; ELISA; TCM
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2023.156309

[Display omitted] •Notopterol ameliorates OA via inhibiting the JAK2/STAT3 and PI3K/AKT pathways.•Notopterol enhances the Nrf2/HO-1 pathway to mediate the expression of downstream proteins.•Notopterol exerts anti-apoptotic effect through the Nrf2/ROS/Bax/Bcl-2 axis in vitro.•Notopterol regulates the increased inflammatory cytokine production in MIA rats.•Notopterol ameliorates cartilage erosion and prevent the process of osteoarthritis. Osteoarthritis (OA) is a prevalent degenerative joint disorder caused by the progressive destruction of cartilage and inflammation in the articular cavity. Studies have proved that the inhibition of articular cartilage destruction and generation of inflammatory factors can be effective strategies for treating OA. Notopterol (NOT) is a quality control index of Notopterygium incisum Ting ex H. T. Chang (N. incisum) with anti-inflammatory, antioxidant, and analgesic activities. Moreover, NOT has been used for many years to treat joint diseases. A study using human C28/I2 cells suggested that NOT down-regulated the hypersecretion of inflammatory mediators and alleviated the degradation of the extracellular matrix (ECM). In addition, NOT decreased the overproduction of reactive oxygen species (ROS) and chondrocyte apoptosis through the nuclear factor erythroid-2–related factor 2 (Nrf2) signaling pathway. NOT exerted a chondroprotective effect by partly inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways and regulating the nuclear factor Nrf2/heme oxygenase-1(HO-1) signaling pathway. In vivo, NOT improved the destruction of articular cartilage in a rat OA model, which may be related to the inhibition of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and IL-12 expressions in synovial fluid. In summary, these results showed that NOT alleviated the progression of OA and is expected to become a new therapy for treating OA clinically.